Fibrin Glue Improves the Therapeutic Effect of MSCs by Sustaining Survival and Paracrine Function

Abstract

Fibrin glue has been widely investigated as a cell delivery vehicle for improving the therapeutic effects of mesenchymal stem cells (MSCs). Implanted MSCs produce their therapeutic effects by secreting paracrine factors and by replacing damaged tissues after differentiation. While the influence of fibrin glue on the differentiation potential of MSCs has been well documented, its effect on paracrine function of MSCs is largely unknown. Herein we investigated the influence of fibrin glue on the paracrine effects of MSCs. MSCs were isolated from human adipose tissue. The effects of fibrin glue on survival, migration, secretion of growth factors, and immune suppression of MSCs were investigated in vitro. MSCs in fibrin glue survived and secreted growth factors such as the vascular endothelial growth factor (VEGF) and hepatocyte growth factor (HGF) over 14 days. VEGF and immune modulators, including the transforming growth factor (TGF)-b1 and prostaglandin E 2 , secreted from MSCs in fibrin glue significantly increased under inflammatory conditions. Thus, MSCs in fibrin glue effectively suppressed immune reactions. In addition, fibrin glue protected the MSCs from oxidative stress and prevented human dermal fibroblast death induced by exposure to extreme stress. In contrast, MSCs within fibrin glue hardly migrated. These results suggest that fibrin glue may sustain survival of implanted MSCs and their paracrine function. Our results provide a mechanistic data to allow further development of MSCs with fibrin glue as a clinical treatment.

Long-Term Results of Adipose-Derived Stem Cell Therapy for the Treatment of Crohn's Fistula

“…The ASCs injected with fibrin glue may have a long‐term synergistic effect with cells injected under the subepithelial layer of the fistula tract. ASCs in fibrin glue matrix effectively release growth factors to enhance wound healing and soluble factors to inhibit immune response by suppressing both T‐cell proliferation and secretion of proinflammatory cytokines from the activated T cells, although cells in fibrin glue matrix may not migrate to the tissue [29]. In addition, the ASCs used in our clinical trial may have different characteristics than those of other clinical trials, even if MSCs were harvested from the same adipose tissue.…”

A prosurvival and proangiogenic stem cell delivery system to promote ischemic limb regeneration

“…They may also provide paracrine effects for vascularization and muscle regeneration. MSCs are known to secrete angiogenic growth factors like VEGF, bFGF and PDGF for vascularization, and IGF-1 for promyogenesis [76, 77]. However, since the cell survival in this group is low (Figure 5), the improvement on blood perfusion recovery and muscle regeneration was limited.…”

Effect of Fibrin Formulation on Initial Strength of Tendon Repair and Migration of Bone Marrow Stromal Cells in Vitro

“…Matrix stiffness can drive the stromal cell lineage and differentiation 32,33 . Kim et al similarly reported that mesenchymal stem cells maintained a rounded shape in fibrin gel with a higher, nonphysiological concentration of fibrinogen (127 to 256 mg/mL) 34 . In contrast, our physiological controls, as well as our low-low and low-high groups, showed a spindle-shape cell morphology, which reflects the morphology of tenocytes 35,36 .…”